WO2025111313A1 - Tablet and method of marking a tablet - Google Patents

Abstract

A compressed mass is provided including a marking formulation including a marking component. The marking component includes a metal oxide. Laser irradiation is applied to the tablet at a wavelength of about 200 nm to about 400 nm, causing the marking component to change color. A method of marking and marking formulation is also provided.

Description

34896-613 Tablet and Method of Marking a Tablet Cross Reference to Related Application(s) [0001] The present application claims priority to U.S. Provisional Application No. 63/601,551 filed on November 21, 2023. The entire contents of which are incorporated in its entirety. Technical Field of the Invention [0002] The present invention relates to a tablet, wherein the tablet includes a marking formulation including a marking component. More specifically, the present invention relates to applying laser irradiation to a softgel capsule at a wavelength of about 100 nm to about 400 nm, causing the marking component to change color. Background of the Invention [0003] In the pharmaceutical industry, it is good manufacturing practice to mark capsules to determine the type of product, the dose, the manufacturer, and other identifying information. There are several methods that can be used to mark tablets. The methods are used to mark the tablet skin/surface. [0004] Some of these methods are ink printing, or by UV laser. During the ink printing method, ink may be placed on the tablet surface by different methods, such as ink jet, offset, or pad printing. A variety of colors may be used in the ink printing method. The ink printing method has its disadvantages. For example, this method touches the surface of the tablet. Because ink is soluble with certain solvents, it can be wiped off. The ink can also be wiped off if solvent within the tablet migrates to the tablet surface. [0005] Another common method to mark a tablet is using a UV laser. Typically, titanium dioxide (TiO₂) is added to the compressed mass of the tablet, such that it reacts with the UV laser by changing color. Often times, the reaction of the TiO2 causes the marking to appear dark on the tablet. Recently, TiO₂ has been discouraged from being used in the industry. Therefore, a need exists in the art for an alternative marking component to be used with a UV laser. Objects and Summary of the Invention [0006] In an embodiment of the present invention, a tablet is provided. The tablet may include a compressed mass, wherein the compressed mass includes at least one active pharmaceutical ingredient or a salt thereof, excipient and a marking formulation. The marking formulation may include a marking component. Laser irradiation may be applied to the tablet of the present disclosure at a wavelength of about 100 nm to about 400 nm, causing the marking component to change color and/or change in appearance on the surface of the tablet. [0007] In an embodiment, the marking component may include a metal oxide. In some embodiments, the metal oxide may include iron oxide. The iron oxide may include iron oxide red, iron oxide yellow, iron oxide brown, iron oxide black, iron oxide blue, iron oxide green, or a combination thereof. [0008] In some embodiments, the marking formulation may be substantially free of titanium dioxide. In some embodiments, the marking formulation does not include titanium dioxide. [0009] In some embodiments, the laser irradiation may be applied to the tablet or compressed mass at a wavelength of about 300 nm to about 375 nm. In an embodiment, the laser irradiation may be achieved using a UV laser. [0010] In another embodiment of the present disclosure, a method for marking a tablet or compressed mass is provided. The method may include irradiating a compressed mass with a laser, where the compressed mass may include a marking formulation having a marking component that does not include titanium dioxide. In some embodiments, the marking component may be substantially free of titanium dioxide. [0011] In some embodiments of the method, the irradiating may be performed using a wavelength below about 400 nm. In some embodiments, the irradiating may be performed using a wavelength of about 100 nm, about 150 nm to about 400 nm, about 200 nm to about 350 nm, or about 250 nm to about 300 nm. In some embodiments, the irradiating may be performed using a UV laser. [0012] In some embodiments of the method, after irradiating the compressed mass, the marking component undergoes a color change and/or a change in appearance on the surface. [0013] In another embodiment of the present disclosure, a marking formulation is provided. The marking formulation may include a marking component including a metal oxide. Laser irradiation may be applied to the marking formulation at a wavelength of about 100 nm to about 400 nm, causing the marking component to change color and/or appearance. [0014] In an embodiment of the marking formulation, the metal oxide may include iron oxide. In some embodiments, the iron oxide may include iron oxide red, iron oxide yellow, iron oxide brown, iron oxide black, iron oxide blue, iron oxide green, or a combination thereof. [0015] In some embodiments of the marking formulation, the marking component may be included in an amount of about 0.001 wt% to about 10 wt%, about 0.005 wt% to about 9 wt%, about 0.01 wt% to about 8 wt%, about 0.05 wt% to about 7 wt%, about 0.1 wt% to about 6 wt%, about 0.5 wt% to about 5 wt%, about 1 wt% to about 4 wt%, about 1.5 wt% to about 3 wt%, or about 2 wt% to about 2.5 wt%, based on a total weight of the marking formulation. [0016] In some embodiments of the marking formulation, the metal oxide may be included in an amount of about 1 gram to about 5 grams, about 1.2 grams to about 4.5 grams, about 1.4 grams to about 4 grams, about 1.6 grams to about 3.5 grams, about 1.8 grams to about 3 grams, or about 2 grams to about 2.5 grams, based on 100 grams of total weight of the marking formulation. [0017] In some embodiments, the marking formulation is substantially free of titanium dioxide. In other embodiments, the marking formulation does not include titanium dioxide. In some embodiments, the marking formulation may further include water. Brief Description of the Drawings [0018] The disclosure described herein is illustrated by way of example and not by way of limitation in the accompany figure. [0019] Figure 1 represents the results of a laser irradiation test according to an embodiment of the present disclosure. Detailed Description [0020] The detailed description set forth below is intended to merely as a description of the presently preferred embodiments of the invention, and is not intended to represent the only form in which the present invention may constructed or utilized. The description sets forth the functions, means, and methods of implementing the invention in connection with the illustrated embodiments. It is to be understood, however, that the same or equivalent functions and features may be accomplished by different embodiments that are also intended to be encompassed within the spirit and scope of the claims. [0021] As used herein, the singular forms “a,” “an,” and “the” include plural references unless the context clearly indicates otherwise. Thus, for example, reference to “an active pharmaceutical ingredient” includes a single active pharmaceutical ingredient as well as a mixture of two or more different active pharmaceutical ingredients, and reference to an “excipient” includes a single excipient as well as a mixture of two or more different excipients, and the like. [0022] As used herein, the term “about” in connection with a measured quantity, refers to the normal variations in that measured quantity, as expected by one of ordinary skill in the art in making the measurement and exercising a level of care commensurate with the objective of measurement and the precision of the measuring equipment. In certain embodiments, the term “about” includes the recited number ±5%, such that “about 10” would include from 9.5 to 10.5. [0023] Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. [0024] The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to illuminate certain materials and methods and does not pose a limitation on scope. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the disclosed materials and methods. [0025] As used herein, the terms “active agent,” “active ingredient,” “active pharmaceutical ingredient,” “API,” and “drug” refer to any material that is intended to produce a therapeutic, prophylactic, or other intended effect, whether or not approved by a government agency for that purpose. These terms with respect to specific agents include all pharmaceutically active agents, all pharmaceutically acceptable salts thereof, complexes, stereoisomers, crystalline forms, co-crystals, ether, esters, hydrates, solvates, and mixtures thereof, where the form is pharmaceutically active. [0026] As used herein, the term “color change” or “change color” refers to a component that may change appearance including, but not limited to black, white, or grey. [0027] As used herein, “free or substantially free” refers to a composition that comprises less than about 1 wt%, less than about 0.5 wt%, less than about 0.25 wt%, less than about 0.1 wt%, less than about 0.05 wt%, less than about 0.01 wt%, or 0 wt% of the component. [0028] In certain embodiments, the present invention is directed to a compressed mass, e.g. a tablet, that may include a marking formulating including a marking component, wherein laser irradiation is applied to the compressed mass at a wavelength of about 100 nm to about 400 nm causing the marking component to change color and/or appearance on a surface of the compressed mass. In certain embodiments, the compressed mass, e.g. tablet, comprises a pharmaceutically active agent. [0029] In some embodiments, the marking component may include a metal oxide. In certain embodiments, the metal oxide may include an iron oxide. The iron oxide may be an iron oxide red, iron oxide yellow, iron oxide black, iron oxide brown, iron oxide blue, iron oxide green, or a combination thereof. In certain embodiments, the marking component does not include titanium dioxide. In other embodiments of the compressed mass, the marking component is substantially free of titanium dioxide. [0030] In some embodiments of tablet/compressed mass, the laser irradiation is achieved by using a UV laser. Without being limited to a theory, the inventors believe that the UV laser reacts with the marking component in the compressed mass and causes a color change and/or a change in appearance through the light of the UV laser. In some embodiments, the laser irradiation may be applied to the compressed mass at a wavelength of about 100 nm, about 110 nm, about 120 nm, about 130 nm, about 140 nm, about 150 nm, about 160 nm, about 170 nm, about 180 nm, about 190 nm, about 200 nm, about 210 nm, about 220 nm, about 230 nm, about 240 nm, about 250 nm, about 260 nm, about 270 nm, about 280 nm, about 290 nm, about 300 nm, about 310 nm, about 320 nm, about 330 nm, about 340 nm, about 350 nm, about 360 nm, about 370 nm, about 380 nm, about 390 nm, or about 400 nm, or any value therein. [0031] In some embodiments, the compressed mass may optionally comprise additional agents such as a plasticizer, coloring agents, flavorings agents, sweetening agents, fillers, antioxidants, diluents, pH modifiers or other pharmaceutically acceptable excipients or additives such as synthetic dyes and mineral oxides. [0032] Exemplary suitable coloring agents may include, but not be limited to, colors such as e.g., white, black, yellow, blue, green, pink, red, orange, violet, indigo, and brown. In specific embodiments, the color of the dosage form can indicate the contents (e.g., one or more active ingredients) contained therein. It is to be understood by one of skill in the art that the coloring agent of the compressed mass may be separate and distinct from that of the marking component. [0033] Exemplary suitable flavoring agents may include, but not be limited to, “flavor extract” obtained by extracting a part of a raw material, e.g., animal or plant material, often by using a solvent such as ethanol or water; natural essences obtained by extracting essential oils from the blossoms, fruit, roots, etc., or from the whole plants. [0034] Additional exemplary flavoring agents that may be in the dosage form may include, but not be limited to, breath freshening compounds like menthol, spearmint, and cinnamon, coffee beans, other flavors or fragrances such as fruit flavors (e.g., cherry, orange, grape, etc.), especially those used for oral hygiene, as well as actives used in dental and oral cleansing such as quaternary ammonium bases. The effect of flavors may be enhanced using flavor enhancers like tartaric acid, citric acid, vanillin, or the like. [0035] Exemplary sweetening agents may include, but not be limited to, one or more artificial sweeteners, one or more natural sweeteners, or a combination thereof. Artificial sweeteners include, e.g., acesulfame and its various salts such as the potassium salt (available as Sunett®), alitame, aspartame (available as NutraSweet® and Equal®), salt of aspartame-acesulfame (available as Twinsweet®), neohesperidin dihydrochalcone, naringin dihydrochalcone, dihydrochalcone compounds, neotame, sodium cyclamate, saccharin and its various salts such as the sodium salt (available as Sweet'N Low®), stevia, chloro derivatives of sucrose such as sucralose (available as Kaltame® and Splenda®), and mogrosides. Natural sweeteners include, e.g., glucose, dextrose, invert sugar, fructose, sucrose, glycyrrhizin; monoammonium glycyrrhizinate (sold under the trade name MagnaSweet®); Stevia rebaudiana (Stevioside), natural intensive sweeteners, such as Lo Han Kuo, polyols such as sorbitol, mannitol, xylitol, erythritol, and the like. [0036] The thickening agent may be a starch, a starch derivative or a modified starch. The starch or starch derivative may be hydroxypropylated tapioca starch, hydroxypropylated corn starch, potato starch, or pregelatinized modified corn starches. The modified starch includes such starces as hydroxypropylated starches, acid thinned starches and the like. In general, modified starches are products prepared by chemical treatment of starches, for example, acid treatment starches, enzyme treatment starches, oxidized starches, cross-bonding starches, and other starch derivatives [0037] The buffer and/or an alkalizing agent may be, but is not limited to, ammonium hydroxide, sodium hydroxide, sodium carbonate, sodium citrate, trisodium phosphate and/or disodium phosphate. In one embodiment, the buffer is disodium phosphate. [0038] The compressed mass may further include water, acrylates copolymer, xanthan gum, glycerin, butylene glycol, aminomethyl propanol, aloe barbaensis leaf extract, active ingredient, a lipid, or a combination thereof. [0039] In some embodiments, the lipid may be selected, without limitations, from the group consisting of , almond oil, argan oil, avocado oil, borage seed oil, canola oil, cashew oil, castor oil, hydrogenated castor oil, cocoa butter, coconut oil, colza oil, corn oil, cottonseed oil, grape seed oil, hazelnut oil, hemp oil, hydroxylated lecithin, lecithin, linseed oil, macadamia oil, mango butter, manila oil, mongongo nut oil, olive oil, palm kernel oil, palm oil, peanut oil, pecan oil, perilla oil, pine nut oil, pistachio oil, poppy seed oil, pumpkin seed oil, rice bran oil, safflower oil, sesame oil, shea butter, soybean oil, sunflower oil, hydrogenated vegetable oil, walnut oil, and watermelon seed oil. Other oil and fats may include, but not be limited to, fish oil (omega-3), krill oil, animal or vegetable fats, e.g., in their hydrogenated form, free fatty acids and mono-, di-, and tri-glycerides with C8-, C10-, C12-, C14-, C16-, C18-, C20- and C22-fatty acids, and combinations thereof. [0040] In some embodiments, the antioxidant may be butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), or a combination thereof. [0041] In certain embodiments of the invention, the compressed mass, e.g. tablet, may be spherical, oval, oblong or round. [0042] In another embodiment of the present disclosure, a method for marking a compressed mass is provided. The method may include irradiating a compressed mass with a laser, wherein the compressed mass may include a marking component. [0043] In some embodiments of the method, the irradiating may be performed using a wavelength below about 400 nm. In another embodiment of the method, the irradiating may be performed using a wavelength of about 100 nm, about 150 nm to about 400 nm, about 200 nm to about 350 nm, or about 250 nm to about 300 nm. [0044] In some embodiments of the method, the irradiating may be performed using a UV laser. [0045] In an embodiment of the method, after irradiating the compressed mass, the marking component may undergo a color change. [0046] In an embodiment of the method, the laser may have a power of about 10 watts to about 30 watts, about 15 to about 25 watts, or about 17.5 watts to about 22.5 watts. [0047] In some embodiments of the method, the marking component may include a metal oxide. In certain embodiments, the metal oxide may include an iron oxide. The iron oxide may be an iron oxide red, iron oxide yellow, iron oxide black, iron oxide brown, iron oxide green, iron oxide blue, or a combination thereof. In certain embodiments, the marking component does not include titanium dioxide. In other embodiments of the compressed mass, the marking component is substantially free of titanium dioxide. [0048] Without being limited to a theory, the inventors believe that the UV laser reacts with the marking component in the compressed mass and causes a color change through the light of the UV laser. In some embodiments, the laser irradiation may be applied to the compressed mass at a wavelength of about 100 nm, about 110 nm, about 120 nm, about 130 nm, about 140 nm, about 150 nm, about 160 nm, about 170 nm, about 180 nm, about 190 nm, about 200 nm, about 210 nm, about 220 nm, about 230 nm, about 240 nm, about 250 nm, about 260 nm, about 270 nm, about 280 nm, about 290 nm, about 300 nm, about 310 nm, about 320 nm, about 330 nm, about 340 nm, about 350 nm, about 360 nm, about 370 nm, about 380 nm, about 390 nm, or about 400 nm, or any value therein. [0049] In another embodiment, a marking formulation is provided. The marking formulation may include a marking component. In some embodiments, laser irradiation may be applied to the marking formulation at a wavelength of about 100 nm to about 400 nm, causing the marking component to change color. [0050] In some embodiments, the marking component may include a metal oxide. In certain embodiments, the metal oxide may include an iron oxide. The iron oxide may be an iron oxide red, iron oxide yellow, iron oxide black, iron oxide brown, iron oxide green, iron oxide blue, or a combination thereof. In certain embodiments, the marking component does not include titanium dioxide. In other embodiments of the softgel capsule, the marking component is substantially free of titanium dioxide. [0051] In an embodiment, the marking component may be included in the marking formulation in an amount of 0.001 wt% to about 10 wt%, about 0.005 wt% to about 9 wt%, about 0.01 wt% to about 8 wt%, about 0.05 wt% to about 7 wt%, about 0.1 wt% to about 6 wt%, about 0.5 wt% to about 5 wt%, about 1 wt% to about 4 wt%, about 1.5 wt% to about 3 wt%, or about 2 wt% to about 2.5 wt%, based on a total weight of the marking formulation. In some embodiments, the marking component may be included in an amount of about 0.001 wt%, about 0.002 wt%, about 0.005 wt%, about 0.01 wt%, about 0.05 wt%, about 0.1 wt%, about 0.25 wt%, about 0.5 wt%, about 0.75 wt%, about 1 wt%, about 1.5 wt%, about 2 wt%, about 2.5 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt%, or any value therein, based on the total weight of the marking formulation. [0052] In some embodiments, the metal oxide may be included in an amount of about 1 gram to about 5 grams, about 1.2 grams to about 4.5 grams, about 1.4 grams to about 4 grams, about 1.6 grams to about 3.5 grams, about 1.8 grams to about 3 grams, or about 2 grams to about 2.5 grams, based on 100 grams of the marking formulation. In other embodiments, the metal oxide may be included in the marking formulation in an amount of about 1 gram, about 1.2 grams, about 1.4 grams, about 1.6 grams, about 1.8 grams, about 2 grams, about 2.5 grams, about 3 grams, about 3.5 grams, about 4 grams, about 4.5 grams, or about 5 grams, based on 100 grams of the marking formulation. [0053] In some embodiments, the marking formulation does not include titanium dioxide. In other embodiments, the marking formulation is substantially free of titanium dioxide. [0054] In some embodiments, the marking formulation may include water. [0055] In an embodiment of the marking formulation, laser irradiation may be applied to the marking formulation at a wavelength of about 100 nm to about 400 nm. In some embodiments, the laser irradiation may be applied using a UV laser. [0056] Any pharmaceutically active ingredient may be used for purposes of the present invention. Suitable pharmaceutically active ingredients include, without limitation, analgesics and anti-inflammatory agents, antacids, anthelmintic, anti-arrhythmic agents, anti- bacterial agents, anti-coagulants, anti-depressants, anti-diabetics, anti-diarrheal, anti- epileptics, anti-fungal agents, anti-gout agents, anti-hypertensive agents, anti-malarial, anti- migraine agents, anti-muscarinic agents, anti-neoplastic agents and immunosuppressants, anti-protozoal agents, anti-rheumatics, anti-thyroid agents, antivirals, anxiolytics, sedatives, hypnotics and neuroleptics, beta-blockers, cardiac inotropic agents, corticosteroids, cough suppressants, cytotoxics, decongestants, diuretics, enzymes, anti-parkinsonian agents, gastro- intestinal agents, histamine receptor antagonists, lipid regulating agents, local anesthetics, neuromuscular agents, nitrates and anti-anginal agents, nutritional agents, opioid analgesics, oral vaccines, proteins, peptides and recombinant drugs, sex hormones and contraceptives, spermicides, stimulants, and combinations thereof. [0057] In some embodiments, the active pharmaceutical ingredient may be selected, without limitations, from the group consisting of dabigatran, dronedarone, ticagrelor, iloperidone, ivacaftor, midostaurine, asimadoline, beclomethasone, apremilast, sapacitabine, linsitinib, abiraterone, vitamin D analogs (e.g., calcifediol, calcitriol, paricalcitol, doxercalciferol), COX-2 inhibitors (e.g., celecoxib, valdecoxib, rofecoxib), tacrolimus, testosterone, lubiprostone, pharmaceutically acceptable salts thereof, and combinations thereof. [0058] According to certain embodiments, active agents may include lipid-lowering agents including, but not limited to, statins (e.g., lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin, and pitavastatin), fibrates (e.g, clofibrate, ciprofibrate, bezafibrate, fenofibrate, and gemfibrozil), niacin, bile acid sequestrants, ezetimibe, lomitapide, phytosterols, and the pharmaceutically acceptable salts, hydrates, solvates and prodrugs thereof, mixtures of any of the foregoing, and the like. [0059] Suitable nutraceutical active agents may include, but are not limited to, 5- hydroxytryptophan, acetyl L-carnitine, alpha lipoic acid, alpha-ketoglutarates, bee products, betaine hydrochloride, bovine cartilage, caffeine, cetyl myristoleate, charcoal, chitosan, choline, chondroitin sulfate, coenzyme Q10, collagen, colostrum, creatine, cyanocobalamin (Vitamin 812), dimethylaminoethanol, fumaric acid, germanium sequioxide, glandular products, glucosamine HCI, glucosamine sulfate, hydroxyl methyl butyrate, immunoglobulin, lactic acid, L-Carnitine, liver products, malic acid, maltose-anhydrous, mannose (d- mannose), methyl sulfonyl methane, phytosterols, picolinic acid, pyruvate, red yeast extract, S-adenosylmethionine, selenium yeast, shark cartilage, theobromine, vanadyl sulfate, and yeast. [0060] Suitable nutritional supplement active agents may include vitamins, minerals, fiber, fatty acids, amino acids, herbal supplements or a combination thereof. [0061] Suitable vitamin active agents may include, but are not limited to, the following: ascorbic acid (Vitamin C), B vitamins, biotin, fat soluble vitamins, folic acid, hydroxycitric acid, inositol, mineral ascorbates, mixed tocopherols, niacin (Vitamin B3), orotic acid, para- aminobenzoic acid, panthothenates, panthothenic acid (Vitamin B5), pyridoxine hydrochloride (Vitamin B6), riboflavin (Vitamin B2), synthetic vitamins, thiamine (Vitamin B1), tocotrienols, vitamin A, vitamin D, vitamin E, vitamin F, vitamin K, vitamin oils and oil soluble vitamins. [0062] Suitable herbal supplement active agents may include, but are not limited to, the following: arnica, bilberry, black cohosh, cat's claw, chamomile, echinacea, evening primrose oil, fenugreek, flaxseed, feverfew, garlic, ginger root, ginko biloba, ginseng, goldenrod, hawthorn, kava-kava, licorice, milk thistle, psyllium, rauowolfia, senna, soybean, St. John's wort, saw palmetto, turmeric, valerian. [0063] Minerals active agents may include, but are not limited to, the following: boron, calcium, chelated minerals, chloride, chromium, coated minerals, cobalt, copper, dolomite, iodine, iron, magnesium, manganese, mineral premixes, mineral products, molybdenum, phosphorus, potassium, selenium, sodium, vanadium, malic acid, pyruvate, zinc and other minerals. [0064] Examples of other possible active agents include, but are not limited to, antihistamines (e.g., ranitidine, dimenhydrinate, diphenhydramine, chlorpheniramine and dexchlorpheniramine maleate), non-steroidal anti-inflammatory agents (e.g., aspirin, celecoxib, Cox-2 inhibitors, diclofenac, benoxaprofen, flurbiprofen, fenoprofen, flubufen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, fluprofen, bucloxic acid, indomethacin, sulindac, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac, meclofenamic acid, flufenamic acid, niflumic acid, tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicam, isoxicam, aceclofenac, aloxiprin, azapropazone, benorilate, bromfenac, carprofen, choline magnesium salicylate, diflunisal, etodolac, etoricoxib, faislamine, fenbufen, fenoprofen, flurbiprofen, ibuprofen, indometacin, ketoprofen, ketorolac, lornoxicam, loxoprofen, meloxicam, mefenamic acid, metamizole, methyl salicylate, magnesium salicylate, nabumetone, naproxen, nimesulide, oxyphenbutazone, parecoxib, phenylbutazone, salicyl salicylate, sulindac, sulfinpyrazone, tenoxicam, tiaprofenic acid, tolmetin. pharmaceutically acceptable salts thereof and mixtures thereof) and acetaminophen, anti-emetics (e.g., metoclopramide, methylnaltrexone), anti-epileptics (e.g., phenyloin, meprobmate and nitrazepam), vasodilators (e.g., nifedipine, papaverine, diltiazem and nicardipine), anti-tussive agents and expectorants (e.g. codeine phosphate), anti-asthmatics (e.g. theophylline), antacids, anti-spasmodics (e.g. atropine, scopolamine), antidiabetics (e.g., insulin), diuretics (e.g., ethacrynic acid, bendrofluthiazide), anti-hypotensives (e.g., propranolol, clonidine), antihypertensives (e.g., clonidine, methyldopa), bronchodilatiors (e.g., albuterol), steroids (e.g., hydrocortisone, triamcinolone, prednisone), antibiotics (e.g., tetracycline), antihemorrhoidals, hypnotics, psychotropics, antidiarrheals, mucolytics, sedatives, decongestants (e.g. pseudoephedrine), laxatives, vitamins, stimulants (including appetite suppressants such as phenylpropanolamine) and cannabinoids, as well as pharmaceutically acceptable salts, hydrates, solvates, and prodrugs thereof. [0065] The active agent that may also be a benzodiazepine, barbiturate, stimulants, or mixtures thereof. The term “benzodiazepines” refers to a benzodiazepine and drugs that are derivatives of a benzodiazepine that are able to depress the central nervous system. Benzodiazepines include, but are not limited to, alprazolam, bromazepam, chlordiazepoxide, clorazepate, diazepam, estazolam, flurazepam, halazepam, ketazolam, lorazepam, nitrazepam, oxazepam, prazepam, quazepam, temazepam, triazolam, as well as pharmaceutically acceptable salts, hydrates, solvates, prodrugs and mixtures thereof. Benzodiazepine antagonists that can be used as active agent include, but are not limited to, flumazenil as well as pharmaceutically acceptable salts, hydrates, solvates and mixtures thereof. [0066] The term “barbiturates” refers to sedative-hypnotic drugs derived from barbituric acid (2, 4, 6,-trioxohexahydropyrimidine). Barbiturates include, but are not limited to, amobarbital, aprobarbotal, butabarbital, butalbital, methohexital, mephobarbital, metharbital, pentobarbital, phenobarbital, secobarbital as well as pharmaceutically acceptable salts, hydrates, solvates, prodrugs, and mixtures thereof. Barbiturate antagonists that can be used as active agent include, but are not limited to, amphetamines as well as pharmaceutically acceptable salts, hydrates, solvates and mixtures thereof. [0067] The term “stimulants” includes, but is not limited to, amphetamines such as dextroamphetamine resin complex, dextroamphetamine, methamphetamine, methylphenidate, as well as pharmaceutically acceptable salts, hydrates, and solvates and mixtures thereof. Stimulant antagonists that can be used as active agent include, but are not limited to, benzodiazepines, as well as pharmaceutically acceptable salts, hydrates, solvates and mixtures thereof. [0068] The dosage forms according to the disclosure include various active agents and their pharmaceutically acceptable salts thereof. Pharmaceutically acceptable salts include, but are not limited to, inorganic acid salts such as hydrochloride, hydrobromide, sulfate, phosphate and the like; organic acid salts such as formate, acetate, trifluoroacetate, maleate, tartrate and the like; sulfonates such as methanesulfonate, benzenesulfonate, p-toluenesulfonate, and the like; amino acid salts such as arginate, asparginate, glutamate and the like, and metal salts such as sodium salt, potassium salt, cesium salt and the like; alkaline earth metals such as calcium salt, magnesium salt and the like; organic amine salts such as triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N′-dibenzylethylenediamine salt and the like. EXAMPLES [0069] Sample tablets were prepared including a marking formulation according to an embodiment of the present disclosure. The marking formulation included iron oxide in an amount from 0.05 g to about 2.5 g. Laser irradiation was applied to the tablet at a wavelength of about 100 nm to about 400 nm. As can be seen in Figure 1, it was found that the marking formulation caused a color change in the tablet. Thus, it could be confirmed that a reaction occurs when a laser is applied to the tablet including a marking formulation. [0070] While certain embodiments have been illustrated and described, it should be understood that changes and modifications can be made therein in accordance with ordinary skill in the art without departing from the technology in its broader aspects as defined in the following claims. [0071] The embodiments, illustratively described herein, may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms “comprising,” “including,” “containing,” etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the claimed technology. Additionally, the phrase “consisting essentially of” will be understood to include those elements specifically recited and those additional elements that do not materially affect the basic and novel characteristics of the claimed technology. The phrase “consisting of” excludes any element not specified. [0072] The present disclosure is not to be limited in terms of the particular embodiments described in this application. Many modifications and variations can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and compositions within the scope of the disclosure, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the appended claims. The present disclosure is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled. It is to be understood that this disclosure is not limited to particular methods, reagents, compounds, or compositions, which can of course vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. [0073] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group. [0074] As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like, include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member.

Claims

What is claimed: 1. A compressed mass comprising: an active pharmaceutical ingredient; an excipient; and a marking formulation including a marking component, wherein laser irradiation is applied to the tablet at a wavelength of about 100 nm to about 400 nm, causing the marking component to change color.

2. The compressed mass of claim 1, wherein the marking component comprises a metal oxide.

3. The compressed mass of claim 2, wherein the metal oxide comprises iron oxide.

4. The compressed mass of claim 3, wherein the iron oxide is iron oxide red, iron oxide yellow, iron oxide brown, iron oxide black, iron oxide green, iron oxide blue, or combination thereof.

5. The compressed mass of any of the preceding claim, wherein the marking formulation is substantially free of titanium dioxide.

6. The compressed mass of any of the preceding claim, wherein the marking formulation does not include titanium dioxide.

7. The compressed mass of any of the preceding claim, wherein the laser irradiation is applied to the compressed mass at a wavelength of about 300 nm to about 375 nm.

8. The compressed mass of any of the preceding claims, wherein the laser irradiation is achieved using a UV laser.

9. A method for marking a compressed mass comprising: irradiating a compressed mass with a laser, wherein the compressed mass includes a marking formulation having a marking component that is substantially free of titanium dioxide.

10. The method of claim 9, wherein the irradiating is performed using a wavelength below about 400 nm.

11. The method of claim 9, wherein the irradiating is performed using a wavelength of about 150 nm to about 400 nm, about 200 nm to about 350 nm, or about 250 nm to about 300 nm.

12. The method of claim 9, wherein the irradiating is performed using a UV laser.

13. The method of claim 9, wherein after the irradiating of the target, the marking component undergoes a color change.

14. The method of claim 9, wherein the marking component is a metal oxide.

15. The method of claim 14, wherein the metal oxide comprises iron oxide.

16. The method of claim 15, wherein the iron oxide is iron oxide red, iron oxide yellow, iron oxide brown, iron oxide black, iron oxide blue, iron oxide green, or a combination thereof.

17. The method of any one of claims 9-16, wherein the marking formulation does not contain titanium dioxide.

18. A marking formulation comprising: a marking component comprising a metal oxide; wherein laser irradiation is applied to the marking formulation at a wavelength of about 200 nm to about 400 nm, causing the marking component to change color.

19. The marking formulation of claim 18, wherein the metal oxide comprises iron oxide.

20. The marking formulation of claim 19, wherein the iron oxide is iron oxide red, iron oxide yellow, iron oxide brown, iron oxide black, iron oxide green, iron oxide blue, or a combination thereof.

21. The marking formulation of claim 18, wherein the marking component is included in an amount of about 0.001 wt% to about 10 wt%, about 0.005 wt% to about 9 wt%, about 0.01 wt% to about 8 wt%, about 0.05 wt% to about 7 wt%, about 0.1 wt% to about 6 wt%, about 0.5 wt% to about 5 wt%, about 1 wt% to about 4 wt%, about 1.5 wt% to about 3 wt%, or about 2 wt% to about 2.5 wt%, based on a total weight of the marking formulation.

22. The marking formulation of claim 18, wherein the metal oxide is included in an amount of about 0.05 gram to about 5 grams, about 0.1 grams to about 4.5 grams, about 0.2 grams to about 4 grams, about 0.5 grams to about 3.5 grams, about 1 gram to about 3 grams, 1.2 grams to about 2.5 g, or about 1.5 grams to about 2 grams, based on 100 grams of total weight of the marking formulation.

23. The marking formulation of any one of claims 18-22, wherein the marking formulation is substantially free of titanium dioxide.

24. The marking formulation of any one of claims 18-23, wherein the marking formulation does not comprise titanium dioxide.

25. The marking formulation of any one of claims 18-24, further comprising water.

26. The marking formulation of any one of claims 18-25, wherein the laser irradiation is applied using a UV laser.